Abstract: | Primary dysmenorrhea (PD) is a common gynecological disorder. Hitherto, animal models
which recapitulate clinical features of PD have not been fully established. We aimed to
examine whether a pain model in mice could mimic the clinic features of PD. After
pretreated with estradiol benzoate (1 mg/kg/day) intraperitoneally (i.p.) for 3
consecutive days, non-pregnant female Imprinting Control Region mice (6–8 weeks old) was
injected with 0.4 U of oxytocin to induce the stretching or writhing response which was
recorded for a time period of 30 min. During the writhing period, the uterine artery blood
flow alterations were examined by Doppler ultrasound detection. After writhing test, the
uterine morphological changes were observed by hematoxylin and eosin (H&E) staining
histopathology. In addition, enzyme-linked immunosorbent assay kit was used to measure the
levels of prostaglandins F2α/prostaglandins E2
(PGF2α/PGE2) and TXB2 (a metabolite of
TXA2)/6-keto-PGF1α (a metabolite of PGI2) in the
uterine tissue homogenates and plasma, respectively. Western blot analyses were performed
to determine the expressions of oxytocin receptor (OTR), beta2-adrenergic receptor
(beta2-AR), and cyclooxygenase-2 (COX-2) in uterine, which are responsible for the uterine
contraction. The writhing response only occurred in the estrogen pretreated female mice.
The area of uterine myometrium significantly decreased along with the increased thickness
in the oxytocin-induced estrogen pretreated mice model. The uterine artery blood flow
velocity dropped, while the pulsatility index and resistance index slightly increased
after the injection of oxytocin. The PGF2α/PGE2 level significantly
increased and the plasma TXB2/6-keto-PGF1α level significantly
enhanced. Compared with the control group, the uterine histopathology demonstrated
moderate to severe edema of endometrium lamina propria. In consistent with the uterine
morphological changes, a significant reduction of beta2-AR and a significant increase of
OTR and COX-2 in the uterine tissue were observed. The writhing response was caused by the
abnormal contraction of uterus. The uterine spasm and ischemia changes of oxytocin-induced
estrogen pretreated female mice model were similar to the pathology of human PD. We
reported an in vivo mice model, which can be used to study PD and for
clinical therapeutic evaluations. |